Overexpressed long noncoding RNA CPS1-IT alleviates pulmonary arterial hypertension in obstructive sleep apnea by reducing interleukin-1 beta expression via HIF1 transcriptional activity
JOURNAL OF CELLULAR PHYSIOLOGY
Authors: Zhang, Zeming; Li, Zheng; Wang, Yancun; Wei, Li; Chen, Hao
Abstract
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. This study was performed to examine the effects of long noncoding RNA CPS1 intronic transcript 1 (CPS1-IT) on PAH in rat models of obstructive sleep apnea (OSA) through regulating interleukin (IL)-1 beta expression. The OSA models were induced in rats, for determination of the CPS1-IT expression. The binding of CPS1-IT and hypoxia-inducible factor 1 (HIF1) was verified. To analyze the effects of CPS1-IT on PAH, the overexpression vector of CPS1-IT and HIF1, shRNA against IL-1 beta and pyrrolidine dithiocarbamate (PDTC, inhibitor of the NF-kappa B signaling pathway) were injected into rat models, respectively. The blood pressure and activity of biochemical indicators including nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), and lipid peroxide (LPO) were assessed. The expression of IL-1 beta, HIF1, alpha-smooth muscle actin (alpha-SMA), proliferating cell nuclear antigen (PCNA), and fibronectin (FN) was determined. The relationship of CPS1-IT to IL-1 beta and NF-kappa B was evaluated. CPS1-IT was downregulated in the OSA rat model. Overexpressed CPS1-IT increased the activity of NO, NOS, and SOD as well as alpha-SMA expression, whereas decreasing LPO activity and expression of PCNA and FN, whereby PAH was suppressed. Notably, overexpressed CPS1-IT reduced IL-1 beta expression through NF-kappa B signaling pathway via inhibiting the HIF1 transcriptional activity, suggesting a mechanism affecting PAH. To conclude, overexpressed CPS1-IT alleviated PAH in OSA by reducing IL-1 beta expression, the mechanism of which was involved with inhibited HIF1 transcriptional activity and the NF-kappa B signaling pathway.
Evolving Viscous Anisotropy in the Upper Mantle and Its Geodynamic Implications
GEOCHEMISTRY GEOPHYSICS GEOSYSTEMS
Authors: Kiraly, A.; Conrad, C. P.; Hansen, L. N.
Abstract
Asthenospheric shear causes some minerals, particularly olivine, to develop anisotropic textures that can be detected seismically. In laboratory experiments, these textures are also associated with anisotropic viscous behavior, which should be important for geodynamic processes. To examine the role of anisotropic viscosity for asthenospheric deformation, we developed a numerical model of coupled anisotropic texture development and anisotropic viscosity, both calibrated with laboratory measurements of olivine aggregates. This model characterizes the time-dependent coupling between large-scale formation of lattice-preferred orientation (i.e., texture) and changes in asthenospheric viscosity for a series of simple deformation paths that represent upper mantle geodynamic processes. We find that texture development beneath a moving surface plate tends to align the a axes of olivine into the plate motion direction, which weakens the effective viscosity in this direction and increases plate velocity for a given driving force. Our models indicate that the effective viscosity increases for shear in the horizontal direction perpendicular to the a axes. This increase should slow plate motions and new texture development in this perpendicular direction and could impede changes to the plate motion direction for tens of millions of years. However, the same well-developed asthenospheric texture may foster subduction initiation perpendicular to the plate motion and deformations related to transform faults, as shearing on vertical planes seems to be favored across a sublithospheric olivine texture. These end-member cases examining shear deformation in the presence of a well-formed asthenospheric texture illustrate the importance of the mean olivine orientation, and its associated viscous anisotropy, for a variety of geodynamic processes.